The immediate goal of this program is to develop a hyperspectral imaging spectrometer capable of measuring DNA microarrays which simultaneously utilize ten or more fluorophore-labeled nucleic acid probes, at a rate of 500,000 samples per hour. The device will greatly increase the speed and reduce the cost of gene expression profiling and mutation and sequence divergence detection. It is expected that the identification of genes that are specifically expressed in disease states will provides clues into the maintenance of these states and perhaps their etiology. Such information is needed for understanding and diagnosing different forms of cancer, and may ultimately lead to the design of therapeutic agents. It should also improve the analysis of the mechanisms of action and side effects of those drugs. Ultimately, though not part of this program, the long-term objective is to adapt this instrument to directly image multiple- fluorophore-tagged samples of tissues and cells. Such a step will dramatically enhance the ability to define the spatial distribution of many tens of molecules at or below the cellular level of resolution, simultaneously and in situ. This capability should increase the capacity to rapidly and reliably provide an assessment of the disease state from biopsies and other tissue samples, and should ultimately allow a more detailed analysis of the interactions between cancerous and pre-cancerous cells and their normal neighbors. The program is a collaboration between Raytheon Optical Systems and Yale University. It is structured in two phases, R21 and R33. The first is a feasibility and concept definition effort. The specific aims are: to clarify the system requirements for a hyperspectral imager; to validate the design concept, and hence justify progressing to the R33 phase; to define an appropriate test and evaluation program in R33; and to define the scope of sample preparation work required for R33. A major objective will be to demonstrate that hyperspectral unmixingalgorithms developed for earth remote sensing and military reconnaissance are effective in discriminating multiple fluorophores. The second phase is primarily an electro-optical instrument design, manufacture, integration and test effort. However, it also involves the fabrication of DNA microarrays, labeled with suitable fluorophores. At completion, the project will result in two research/development instruments which will be in place at Yale and available to the cancer research community.